Toward Capturing the Exposome: Biomarker Variability

and Co-Exposure Patterns in the Shared Environment

Ming Kei (Jake) Chung1, Rajeshwari Sundaram2, Kurunthachalam Kannan3, Germaine Buck Louis4, Chirag J Patel1
1Department of Biomedical Informatics, Harvard University
2Biostatistics and Bioinformatics Branch, The National Institutes of Health
3Division of Environmental Health Sciences, New York State Department of Health
4Office of the Director, Division of Intramural Population Health Research, The National Institutes of Health

INTRODUCTION Figure 2 (Left)

Exposome correlation globe showing the
Mining the exposome could allow us to discover the dark matter relationships between females, males and
that helps to explain common diseases. However, the exposome couples. Only rs greater than 0.25 and smaller
is a dynamic entity that varies from time-to-time (temporal) and than -0.25 were shown as connections in the
place-to-place (spatial). While it is not possible to track and diagram. Red line denotes positive correlation
assess every subject, unit-level ascertainments of exposures could and dark green line denotes negative one.
be a solution.
Color intensity and line width are proportional
Because family members spend a significant amount of time at to the size of the correlation. Within-class and
home and many known sources of exposures are shared among between-class correlations are shown outside
them (e.g. food and water), we hypothesize that shared and inside of the track respectively.
household could have influential effects 1) on the exposure levels Correlations in couples are indicated by the
and 2) co-exposure patterns between the members. lines linking females and males (i.e. crossing the
vertical-half of the globe).
METHODS
CONCLUSIONS
Study Leveraged 501 pairs of couples from the
Longitudinal Investigation of Fertility and the Although individuals spend a significant
Subjects
Environment Study (2005 to 2009) amount of time at home, shared
environment is not a significant factor
explaining co-variations of 128 chemical
biomarkers.
Used 128 biomarkers from 13 chemical classes
Exposures (Figure 2) Co-exposure patterns of the exposome,
Most are endocrine disrupting chemicals especially for persistent organic EDCs
(EDCs). E.g., polyfluoroalkyl substances (PFASs) (e.g. PCBs), are tightly correlated but
similar in males versus females
separately.
1) Estimated the % variance explained (adjusted
coefficient of determination, R2) by shared
household with model residuals IMPLICATIONS
Statistical
Log(chemical) ~ age + sex +
Analyses total_lipids/ creatinine To study the elusive environment:
2) Estimated the Spearmans rank correlation (rs)
Lipophilicity and persistency of the
with model residuals
chemicals are important factors justifying
Log(chemical) ~ total_lipids/ creatinine
the use of unit-level instead of individual-
based exposure assessment.
Understanding the dense correlations in
RESULTS
the exposome could help to increase the
power of exposome-wide association
study and identify the key disease-
associating entities in mixtures of
exposures.

TOOL

Figure 3 The R code for the exposome globe can be

easily modified to fit for other larger and
Boxplots of rs within different chemical classes. A)
complex exposome-wide correlation
Females; B) Males; and C) Couples. Certain classes contain
analyses. Source code will be publicly
only 1 pair of correlation (paracetamols in females,
available on GitHub (via MIT license) when
paracetamols in males, and cotinine in couples). All
we publish our findings.
represents the grouping by the correlation of all pairs of
chemicals available.
Horizontal line drawn across the chemical classes is equal ACKNOWLEDGEMENTS
Figure 1 to the 95th percentile of the null distribution obtained
from permuting the concentrations of all chemicals.
Summary of the percentage variance explained by the shared
environment. Boxplots of the adjusted coefficient of
determination within different chemical classes are shown.
Shared household explained less than 20% of the total variance in
11 of the 13 EDC classes.

Contact: Jake Chung (jake_chung@hms.harvard.edu; twitter:@jakekei)